Posttraumatic stress disorder (PTSD) and high hostility are significant risk factors for poor health. We have begun to identify a number of behavioral and psychophysiological variables that may contribute to this increased risk. Research in the last funding period (NIMH R01MH62482) indicated, for example, that PTSD veterans smoke more, have higher lipids, report poorer objective sleep and more daily negative affect. Findings that ambulatory heart rate is higher, and blood pressure recovery to a stressful task is slower in hostile veterans with PTSD suggest that the autonomic nervous system may be involved in the increased risk in PTSD veterans with high hostility. We also documented a close association between the severity of PTSD and reduced levels of heart rate variability in women. In addition, individuals with PTSD have reduced sleep duration and sleep efficiency, which may lead to reduced levels of ambulatory heart rate variability. Pilot data from this period also suggest an increased rate of metabolic syndrome in our participants with PTSD. Although previous work has demonstrated a relationship between PTSD and reduced parasympathetic nervous system control of the heart under controlled laboratory conditions, no study has evaluated autonomic responses across a 24-hour period outside the laboratory. Taken together, this program of research suggests that PTSD and hostility increase cardiovascular and metabolic risk factors and may contribute to increased risk of poorer health outcomes and cardiovascular mortality. The proposed study will evaluate whether PTSD in a younger cohort is associated with biomarkers of cardiovascular risk measured from vascular endothelial function, 24-hour heart rate variability, and baroreflex sensitivity, and will determine whether the biomarkers of risk are highest among individuals with PTSD and high hostility. Parallel analyses will evaluate whether PTSD is related to insulin resistance and risk of metabolic syndrome. As depression has also been related to cardiovascular risk factors, we will evaluate the independent effects of PTSD by comparing two groups of patients with PTSD including those with and without co-morbid major depressive disorder. The project goals are to examine: (1) the independent relationship between PTSD and biomarkers of cardiovascular and metabolic disease and (2) the contribution of hostility as a moderator and co-morbid major depressive disorder to the relationship between PTSD and biomarkers of cardiovascular and metabolic disease. Study results will serve to inform development of risk reduction strategies in individuals with PTSD early in the trajectory of their disorder. In addition, this study should significantly advance knowledge about the mechanisms that are involved in the increased risk of mortality associated with PTSD. By evaluating possible mechanisms that may be specific to or amplified in a psychiatric patient sample, we may gain a more complete understanding of the psychopathological mechanisms in health effects of psychiatric disorder. PUBLIC HEALTH RELEVANCE: Posttraumatic stress disorder (PTSD) is a prevalent mental disorder in both men and women, and those with PTSD have a greater risk of cardiovascular and metabolic morbidity and mortality. This study will provide important information on the development of cardiovascular and metabolic disease biomarkers in younger individuals with PTSD.